Description

Biological drug and vaccine manufacturing has quickly become one of the highest-value fields of bioprocess engineering, and many bioprocess engineers are now finding job opportunities that have traditionally gone to chemical engineers. Fundamentals of Modern Bioprocessing addresses this growing demand.

Written by experts well-established in the field, this book connects the principles and applications of bioprocessing engineering to healthcare product manufacturing and expands on areas of opportunity for qualified bioprocess engineers and students. The book is divided into two sections: the first half centers on the engineering fundamentals of bioprocessing; while the second half serves as a handbook offering advice and practical applications.

Focused on the fundamental principles at the core of this discipline, this work outlines every facet of design, component selection, and regulatory concerns. It discusses the purpose of bioprocessing (to produce products suitable for human use), describes the manufacturing technologies related to bioprocessing, and explores the rapid expansion of bioprocess engineering applications relevant to health care product manufacturing. It also considers the future of bioprocessing—the use of disposable components (which is the fastest growing area in the field of bioprocessing) to replace traditional stainless steel.

Fundamentals of Modern Bioprocessing outlines both the principles and applications of bioprocessing engineering related to healthcare product manufacturing. It lays out the basic concepts, definitions, methods and applications of bioprocessing. A single volume comprehensive reference developed to meet the needs of students with a bioprocessing background; it can also be used as a source for professionals in the field.

Reviews

"… destined to become a standard handbook for bioprocess engineers. It provides a detailed discussion of emerging areas, such as disposable bioreactors, that are scarcely covered in the books that are currently available."

—Jules Magda, University of Utah, Salt Lake City, USA

Table of Contents

ENGINEERING FUNDAMENTALS OF BIOPROCESSING

Frontiers of Bioprocessing

Defining Bioprocessing

Current and Emerging Trends in Bioprocess Engineering

Materials Advances

Nanoscale Advances

Bioprocessing for Chemical and Biologic Product Manufacturing

Bioprocessing Leaders Worldwide

Economic Predictions and Careers in Bioprocess Engineering

Skills Needed for Future Bioprocess Engineers

Appendix A: A Time Line of Biotechnology Development

Introduction to Molecular Biology

Introduction

Building Blocks of Life: DNA, RNA, and Proteins

DNA Replication

Transcription

Translation

Genes

Mutations

Chromosome

DNA Cloning

Introduction to Biochemistry

Introduction

DNA Structure

RNA Structure

Protein Structure and Function

Carbohydrates

Lipids, Fats, and Steroids

Basic Metabolic Pathways

Introduction to Cellular Microbiology

Introduction

General Cell Structure

Eukaryotes, Prokaryotes, Archaea, and Viruses

Intracellular Organelles

Cellular Transport

Intracellular Signal Transduction

Reaction Stoichiometry, Thermodynamics, and Kinetics

Introduction

Mass and Energy Balances

Fundamentals of Chemical Reactions

Basic Mass Transfer: Diffusion and Convection

Basic Fluid Dynamics

Basic Thermodynamics

Basic Reaction Kinetics

Kinetics of Enzymes and Cell Growth

Introduction

Basic Michaelis–Menten Kinetics

Michaelis–Menten Kinetics with Inhibition

pH and Transport Limitations

Other Enzyme Kinetics

Prokaryotic and Eukaryotic Growth Models

Advanced Prokaryotic and Eukaryotic Growth Models

Data Management

Introduction

Good Laboratory Practices

Electronic Data Handling

Data Errors

Statistical Analysis

Data Conclusions

Flow Diagrams

Exercises and Solutions

HANDBOOK OF BIOPROCESSING

Elements of Bioprocessing

Introduction

Upstream Processing

Bioreactor

Downstream Processing

Genetically Modified Organisms

Introduction

Cell Line Characterization

Characterization of Cell and Virus Banks

Cell Line Construction

Designing GMCS

Vector

Host Systems

Expression System in E Coli

Configuration of Efficient Expression Vectors

Protein Production

Genetic Manipulations to Improve Yield

Manufacturing Overview

Introduction

Cell Culture Expression Systems

Transgenic Animals

Cell Lines and Characterization

Media

Culture Growth

Extraction, Isolation, and Purification

Capture

Purification

Impurity Removal

Validation

Intermediate Purification

Polishing

Formulation

Process Overview

Tech Transfer and Documentation

Validation

Scale Up

Specific Economy Issues

Process Materials

Environment Control

Good Manufacturing Controls of Active Pharmaceutical Ingredients

Manufacturing Systems and Layout

Cleaning Procedures

Processing and Filling

Laboratory Testing

Laboratory Controls

Documentation

Technical Package

Outsourcing in Biotech Manufacturing

Issues to Discuss

Disposable Bioprocessing Systems

Introduction

Safety of Disposable Systems

Regulatory Matters

Risk Assessment

Disposable Containers

Tank Liners

Mixing Systems

Disposable Bioreactors

Disposable Connectors and Transfers

Disposable Control and Monitoring Systems

Downstream Processing

Filtration

Upstream Processing

Introduction

Bioreactors

Batch Culture

Continuous Culture

Fed-Batch Culture

Perfusion Culture

Suspension Culture

Microcarrier Support

Roller Bottle Culture System

Spinner Flask Culture

Other Scale up Options

Wave Bioreactor

Cell Cube Technology

Rotary Culture System

Media

Scaling and Production Costs

Problem Resolution in Fusion Protein Expression

Downstream Processing

Introduction

Capture

System Suitability

Downstream Processing Systems

Process Flow

Purification

Introduction

Protein Properties

Affinity Chromatography

Immobilized Metal Affinity Chromatography

Anion Exchange Chromatography

Cation Exchange Chromatography

Size Exclusion Chromatography

Reversed Phase Chromatography

Hydroxyapatite Chromatography

Hydrophobic Interaction Chromatography

Scale-up and Optimization

Manufacturing Systems

Bacterial Expression Systems

Genetically Modified Bacteria

Mammalian Cells Manufacturing Systems

Yeast Cell Expression System

Insect Cells Systems

Quality Consideration

Introduction

Management Responsibilities

Resources

Manufacturing Operations

Evaluation Activities

Conclusion

QA Systems

Validation Master Plan

Raw Materials

Column Life

Process

Virus Validation

Testing of Product

In-Process Control

Regulatory Affairs

Regulatory Issues

Protein Degradation

Stability Considerations

Intellectual Property

Introduction

Patenting Systems and Strategies

The Patent Laws

Types of Patent Laws

Anatomy of a Patent

Patentability

Patentability and Technical Information Search

Components of a Patent Application

Inventions of Interest to Pharmaceutical Scientists

Biotechnology Inventions

Patenting Strategies

Bibliography

About the Authors

Sarfaraz K. Niazi, Ph.D., is the founding executive chairman of Therapeutic Proteins International, LLC. He began his career teaching pharmacy at the University of Illinois, where he was a tenured professor, before entering the pharmaceutical industry with Abbott International, where he became a Volwiler fellow. Dr. Niazi is a licensed practitioner of patent law, has published numerous books and papers, and has been recognized with several awards for his contributions to science and literature. His inventions, philanthropy, and passion for science, literature, music, and photography have also been documented in publications such as Forbes, Chicago Tribune, and Crain’s Chicago Business.

Justin L. Brown, Ph.D., joined the biomedical engineering faculty of The Pennsylvania State University in 2010. Prior to joining Penn State, Dr. Brown spent seven years at the University of Virginia where he obtained his Ph.D. in biomedical engineering and completed a postdoctoral fellowship in cell and microbiology. His current research interests focus on exploring the signaling cascades and lineage commitment of mesenchymal stem cells in response to biomaterial surfaces that have potential for translation to clinical strategies. Dr. Brown’s lab applies both a reductionist and high-throughput systems approach towards understanding the mechanistic cellular response to extracellular biomaterial geometries.